INHIBITION OF RAT HEPATIC-MICROSOMAL PROPRANOLOL METABOLISM BY A COVALENTLY BOUND REACTIVE METABOLITE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 27  (2) , 211-222
Abstract
Repetitive oral propranolol administration to rats (100 mg/kg per day for 5 days) caused an 80% inhibition of propranolol Type I spectral binding capacity. This paralleled a similar reduction in the microsomal metabolism of propranolol when incubated at low substrate concentrations (< 2 .mu.M). Propranolol was converted both in vitro and in vivo by a microsomal mixed function oxidase to a reactive intermediate metabolite capable of covalently binding with microsomal macromolecules. Covalent binding of the intermediate to the catalytic site of a form of cytochrome P-450 that metabolizes propranolol may account for the marked inhibition of propranolol metabolism seen after propranolol pretreatment.